Quantitative study of mitochondrial complex I in platelets of parkinsonian patients.
Activity of mitochondrial enzyme complex I (NADH-ubiquinone oxidoreductase) is reduced in the substantia nigra of patients with Parkinson's disease (PD). A less pronounced decrease in the activity of this enzyme has also been reported in platelets of PD patients. To obtain quantitative information on platelet complex I in PD, we studied platelet complex I in 16 PD patients and 16 age-matched controls by using a newly developed technique based on the binding of [3H]dihydrorotenone ([3H]DHR), an analog of the pesticide rotenone, to complex I. We also investigated the inhibitory effect of MPP+ (1-methyl-4-phenyl-pyridinium) on [3H]DHR specific binding to platelet complex I. PD patients and controls showed similar levels of [3H]DHR specific binding; preincubation of platelets with MPP+ caused the same degree of inhibition of [3H]DHR specific binding in the two groups. In PD patients, we observed a direct correlation between MPP+-induced inhibition of [3H]DHR specific binding and the daily intake of levodopa, which may be related to drug-induced changes in the transport of MPP+ into the platelet or in its binding to complex I. These findings demonstrate that the reported reduction in complex I activity in platelets of PD patients can not be accounted for by an abnormality at the level of the rotenone binding site (putatively the ND-1 gene product), although they do not exclude differences in complex I activity between PD patients and controls.
Blandini
F
F
C. Mondino Neurological Institute, University of Pavia, Italy.
Nappi
G
G
Greenamyre
J T
JT
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D016022:Case-Control Studies; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042967:Electron Transport Complex I; D005260:Female; D006801:Humans; D007306:Insecticides / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D009247:NADH, NADPH Oxidoreductases / Q000097:blood* / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology*; D010300:Parkinson Disease / Q000097:blood / Q000201:enzymology*; D011869:Radioligand Assay; D012402:Rotenone / Q000031:analogs & derivatives* / Q000378:metabolism
D015259:Dopamine Agents; D007306:Insecticides; D009498:Neurotoxins; D012402:Rotenone; C044985:1',2'-dihydrorotenone; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I; D015655:1-Methyl-4-phenylpyridinium